Immune-like Phagocyte Activity in the Social Amoeba

Chen, Guokai; Zhuchenko, Olga; Kuspa, Adam

doi:10.1126/science.1143991

Cited by 180 publications

(199 citation statements)

References 32 publications

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“…A recent study has revealed a further, unexpected, and quite remarkable anatomical feature of the slug (Chen et al 2007). The study identified cells scattered within the slug, the Sentinel cells (S cells), that phagocytose bacteria and sequester toxins.…”

Section: Developmental Markers and Prestalk And Stalk Cell Subtypesmentioning

confidence: 95%

Dictyostelium Finds New Roles to Model

Williams

2010

Genetics

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Any established or aspiring model organism must justify itself using two criteria: does the model organism offer experimental advantages not offered by competing systems? And will any discoveries made using the model be of wider relevance? This review addresses these issues for the social amoeba Dictyostelium and highlights some of the organisms more recent applications. These cover a remarkably wide gamut, ranging from sociobiological to medical research with much else in between.

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Section: Developmental Markers and Prestalk And Stalk Cell Subtypesmentioning

confidence: 95%

Dictyostelium Finds New Roles to Model

Williams

2010

Genetics

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“…During development, a small population of phagocytic cells serves a protective roll to sequester toxic components. These 'sentinel' cells exhibit immune-like properties (Chen et al, 2007), and this might suggest a shared function of PS/-secretase in these cells and in mammalian macrophages.…”

Section: Phagocytosismentioning

confidence: 99%

Dictyostelium possesses highly diverged presenilin/γ-secretase that regulates growth and cell-fate specification and can accurately process human APP: a system for functional studies of the presenilin/γ-secretase complex

McMains

Myre

Kreppel

et al. 2010

Disease Models &Amp; Mechanisms

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SUMMARY Presenilin (PS) is the catalytic moiety of the γ-secretase complex. PS and other γ-secretase components are well conserved among metazoa, but their presence and function in more-distant species are not resolved. Because inappropriate γ-secretase processing of amyloid precursor protein (APP) in humans is associated with familial Alzheimer’s disease, understanding essential elements within each γ-secretase component is crucial to functional studies. Diverged proteins have been identified in primitive plants but experiments have failed to demonstrate γ-secretase activity. We have identified highly diverged orthologs for each γ-secretase component in the ancient eukaryote Dictyostelium, which lacks equivalents of APP, Notch and other characterized PS/γ-secretase substrates. We show that wild-type (WT) Dictyostelium is capable of amyloidogenic processing of ectopically expressed human APP to generate amyloid-β peptides Aβ40 and Aβ42; strains deficient in γ-secretase cannot produce Aβ peptides but accumulate processed intermediates of APP that co-migrate with the C-terminal fragments α- and β-CTF of APP that are found in mammalian cells. We further demonstrate that Dictyostelium requires PS for phagocytosis and cell-fate specification in a cell-autonomous manner, and show that regulation of phagocytosis requires an active γ-secretase, a pathway suggested, but not proven, to occur in mammalian and Drosophila cells. Our results indicate that PS signaling is an ancient process that arose prior to metazoan radiation, perhaps independently of Notch. Dictyostelium might serve to identify novel PS/γ-secretase signaling targets and provide a unique system for high-throughput screening of small-molecule libraries to select new therapeutic targets for diseases associated with this pathway.

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“…The slug itself will not fall apart on encountering bacteria. Some shed cells are former sentinel cells, full of toxins and bacteria mopped up as they traversed through the slug (45).…”

Section: Dictyostelium Discoideum As a Model System For Cooperationmentioning

confidence: 99%

Evolution of cooperation and control of cheating in a social microbe

Strassmann

Queller

2011

Proc. Natl. Acad. Sci. U.S.A.

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Much of what we know about the evolution of altruism comes from animals. Here, we show that studying a microbe has yielded unique insights, particularly in understanding how social cheaters are controlled. The social stage of Dictylostelium discoideum occurs when the amoebae run out of their bacterial prey and aggregate into a multicellular, motile slug. This slug forms a fruiting body in which about a fifth of cells die to form a stalk that supports the remaining cells as they form hardy dispersal-ready spores. Because this social stage forms from aggregation, it is analogous to a social group, or a chimeric multicellular organism, and is vulnerable to internal conflict. Advances in cell labeling, microscopy, single-gene knockouts, and genomics, as well as the results of decades of study of D. discoideum as a model for development, allow us to explore the genetic basis of social contests and control of cheaters in unprecedented detail. Cheaters are limited from exploiting other clones by high relatedness, kin discrimination, pleiotropy, noble resistance, and lottery-like role assignment. The active nature of these limits is reflected in the elevated rates of change in social genes compared with nonsocial genes. Despite control of cheaters, some conflict is still expressed in chimeras, with slower movement of slugs, slightly decreased investment in stalk compared with spore cells, and differential contributions to stalk and spores. D. discoideum is rapidly becoming a model system of choice for molecular studies of social evolution.kin selection | kin recognition | multicellularity | major transitions

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Immune-like Phagocyte Activity in the Social Amoeba

Cited by 180 publications

References 32 publications

Dictyostelium Finds New Roles to Model

Dictyostelium Finds New Roles to Model

Dictyostelium possesses highly diverged presenilin/γ-secretase that regulates growth and cell-fate specification and can accurately process human APP: a system for functional studies of the presenilin/γ-secretase complex

Evolution of cooperation and control of cheating in a social microbe

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